Seizure-related opening of the blood-brain barrier induced by soman: possible correlation with the acute neuropathology observed in poisoned rats.
In rats poisoned with soman, an irreversible organophosphate anticholinesterase, acute changes in blood-brain barrier (BBB) permeability to proteins were investigated, using Evans Blue (EB)-labelled serum albumin and plasmatic gamma-immunoglobulin G (IgG) as indicators. Confirming previously published data, soman produced a conspicuous seizure-related and reversible BBB opening which was greatest after 30 to 60 min of paroxysmal electroencephalographic (EEG) discharges when signs of cerebral hyperactivity (epileptic EEG pattern, hyperoxia) were also at their height. Topographically, the protein leakage was bilateral and restricted to anatomically defined brain structures, some of which being thereafter sites of parenchymal edema and neuronal damage. In these areas (e.g., the thalamus), the edema is probably, at least in part, "vasogenic" in origin, and the possible contribution of the transient BBB opening to the neuronal lesions was questioned. On the other hand, the hippocampus, a region preferentially affected by the soman-induced acute neuropathology, was always free of any protein leakage, suggesting that the edema is unrelated to vascular damage and "cytotoxic" in nature. Finally, no topographic relationship was shown to exist between the increase in cerebrovascular permeability produced by soman and the histochemically-detected inhibition of the parenchymal total cholinesterases (ChE) or endothelial butyrylcholinesterase (BuChE).
Carpentier
P
P
Centre de Recherches du Service de Santé des Armées, Unité de Neurotoxicologie, La Tronche, France.
Delamanche
I S
IS
Le Bert
M
M
Blanchet
G
G
Bouchaud
C
C
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000506:poisoning; D002802:Cholinesterases / Q000378:metabolism; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D008856:Microscopy, Fluorescence; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D012999:Soman / Q000506:poisoning*
D001798:Blood Proteins; D002800:Cholinesterase Inhibitors; D012999:Soman; D002802:Cholinesterases; D010100:Oxygen